Neonatal treatment of CINCA syndrome.

Annette Von Scheven-Gête,Matthias Roth-Kleiner,Bernard Vaudaux,Yan Paccaud,Gerald Berthet,Michael Hofer,Yvan Mivelaz

doi:10.1186/1546-0096-12-52

Abstract

Chronic Infantile Neurological Cutaneous Articular (CINCA) syndrome, also called Neonatal Onset Multisystem Inflammatory Disease (NOMID) is a chronic disease with early onset affecting mainly the central nervous system, bones and joints and may lead to permanent damage. We report two preterm infants with severe CINCA syndrome treated by anti-interleukin-1 in the neonatal period, although, so far, no experience with this treatment in infants younger than three months of age has been reported. A review of the literature was performed with focus on treatment and neonatal features of CINCA syndrome.Case reportTwo cases suspected to have CINCA syndrome were put on treatment with anakinra in the early neonatal period due to severe clinical presentation. We observed a rapid and persistent decline of clinical signs and systemic inflammation and good drug tolerance. Diagnosis was confirmed in both cases by mutations in the NLRP3/CIAS1-gene coding for cryopyrin. As particular neonatal clinical signs polyhydramnios and endocardial overgrowth are to be mentioned.ConclusionWe strongly suggest that specific treatment targeting interleukin-1 activity should be started early. Being well tolerated, it can be introduced already in neonates presenting clinical signs of severe CINCA syndrome in order to rapidly control inflammation and to prevent life-long disability.

Highlights

Chronic Infantile Neurological Cutaneous Articular syndrome (CINCA) (OMIM 607’115), called Neonatal Onset Multisystem Inflammatory Disease (NOMID), is the most severe form of the Cryopyrin-Associated Periodic Syndromes (CAPS), a continuum of diseases with mutations of the CIAS1-gene called NLRP3, coding for cryopyrin
We strongly suggest that specific treatment targeting interleukin-1 activity should be started early
The first manifestations of CINCA syndrome may be present at birth, neonatal diagnosis is rare and no experience with specific treatment targeting interleukin-1 activity before three months of age is described in the literature [3,4,5,6,7,8,9]

Summary

Conclusion

The clinical triad of cutaneous rash, arthritis and meningitis-like symptoms, associated with severe inflammation without infection should point, already in newborn infants, towards the diagnosis of CINCA syndrome. These two cases suggest that, in severe situations, treatment can be initiated safely in neonates in order to prevent irreversible organ damage and life-long disability. Authors’ contributions YP cared for the first patient and drafted most of the manuscript. MRK was the senior physician responsible for care of the first patient and was involved in drafting and revision of the manuscript. Authors’ information Yan Paccaud and Gerald Berthet equal contribution as first authors. Matthias Roth-Kleiner and Michael Hofer equal contribution as last authors

Background

Discussion

Findings

Kuemmerle-Deschner JB

Goldbach-Mansky R